Wet/dry automatic injector assembly

ABSTRACT

An automatic medicament injector having a compartment for a dry medicament component and a compartment for a wet medicament component. The two compartments are separated by a seal structure that has a plug that is moved from a sealing position into a mixing position when the device is activated. The seal structure includes a wiper that scrapes the interior walls in the dry component compartment to prevent the dry component from accumulating at the seal/glass interface. A tapered insert “funnels” the mixed medicament components to an attached needle assembly, but can be removed when the device is filled. A filter is provided between the medicament compartments and the needle assembly. A chamber between the filter and the needle assembly allows for better flow through the filter. An actuation assembly drives the plug into the mixing position and forces the mixed medicament through the needle and into the user.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S. patentapplication Ser. No. 09/897,422, filed on Jul. 3, 2001, and Ser. No.09/972,202, filed on Oct. 9, 2001. Those two applications claim priorityto U.S. Provisional Application Nos. 60/238,458, 60/238,448, and60/238,447, all filed on Oct. 10, 2000. The contents of all of thoseapplications are incorporated by reference herein in their entireties.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to drug delivery devices. Moreparticularly, the present invention relates to automatic injectorassemblies capable of mixing two components of a medicament and thendelivering the mixed medicament to an injection site.

[0004] 2. Description of Related Art

[0005] An automatic injector is a device that enables intramuscular (IM)or subcutaneous administration of a dosage of medicament. Generally, themedicament is stored as a liquid formulation which is then injectedintramuscularly. An advantage of automatic injectors is that theycontain a measured dosage of a liquid medicament in a sealed sterilecartridge. As such, automatic injectors allow for quick and simple IMinjection of a liquid medicament in emergency situations without theneed for measuring dosages. Another advantage of automatic injectors isthat the administration of the medicament is accomplished without theuser initially seeing the hypodermic needle through which the medicamentis delivered, and without requiring the user to manually force theneedle into the patient. This is particularly advantageous when themedicament is being self-administered.

[0006] There are drawbacks associated with the long-term storage ofmedicament in a liquid formulation. For instance, some medicaments arenot stable in solution and thus have a shorter shelf life than theirsolid counterparts. To address this concern, automatic injectors havebeen developed which store the medicament in solid form and mix thesolid medicament with a liquid solution immediately prior to injection.These injectors, disclosed for example in U.S. Reissue Pat. No. 35,986,entitled “Multiple Chamber Automatic Injector,” (the disclosure of whichis incorporated herein specifically by reference), however, require theuser of the injector to manually rupture a sealing member between thesolid and liquid components and then manually shake the injector body toexpedite dissolution of the solid component prior to injection. Thisincreases the time needed to administer a dose of the medicament.However, rapid delivery of the medicament is needed in many emergencymedical situations (e.g., nerve gas and chemical agent poisoning). Otherwet/dry injection devices have been expensive to manufacture or providedunsatisfactory mixing of components prior to injection. Therefore, thereis a need for a cost-effective automatic injector that stores medicamentin solid form that does not require manual premixing by the user.

SUMMARY OF THE INVENTION

[0007] One aspect of the invention relates to an automatic injectiondevice containing a pre-loaded charge of medicament for automaticallyself-administering the medicament upon actuation thereof. The automaticinjection device comprises a housing and a medicament chamber disposedin the housing. The medicament chamber includes a first compartmentcontaining a dry medicament portion and a second compartment containinga wet medicament portion to be mixed with the dry medicament portion. Aseal structure is provided between the first compartment and the secondcompartment. The seal structure is initially in a sealing condition thatmaintains the first compartment separate from the second compartment.The seal structure includes at least one flow path and an annular wiperportion disposed at the front end of the seal structure and positionedto movingly engage inner walls of the first compartment as the sealstructure is moved through the first compartment. The wiper portion isconfigured to direct dry medicament particles engaged with the innerwalls of the medicament chamber radially inwardly as the seal structuremoves through the first compartment. The seal structure is converted toa mixing condition as a result of activation of the device. Theautomatic injection device also includes a needle assembly and anactivation assembly. The needle assembly dispenses the mixed medicamentportions from the medicament chamber. The activation assembly is carriedby the housing and includes a stored energy source. Activation of theactivation assembly releases the stored energy from the stored energysource, causing the seal structure to be converted from the sealingcondition to the mixing condition, and thereby causing or allowing themedicament portions to be mixed and forced through the needle assembly.

[0008] Another aspect of the invention relates to an automatic injectiondevice containing a pre-loaded charge of medicament for automaticallyself-administering the medicament upon actuation thereof. The automaticinjection device comprises a housing and a medicament chamber disposedin the housing. The medicament chamber includes a first compartmentcontaining a first medicament portion, and a second compartmentcontaining a second medicament portion to be mixed with the firstmedicament portion. The device also includes a seal structure betweenthe first compartment and the second compartment. The seal structure isinitially in a sealing condition that maintains the first compartmentseparate from the second compartment, and is converted to a mixingcondition as a result of activation of the device. A needle assemblydispenses the medicament charge from the medicament chamber. The needleassembly has a rearward opening with a diameter that is less than adiameter of the medicament chamber. An insert is mounted in a forwardend of the medicament chamber adjacent the needle assembly. The insertdefines a tapering flow pathway that tapers radially inwardly as itextends axially forwardly. An activation assembly is carried by thehousing and includes a stored energy source. Activation of theactivation assembly releases the stored energy from the stored energysource, causing the seal structure to be converted from the sealingcondition to the mixing condition, and thereby causing or allowing thefirst and second medicament portions to be mixed, directed by the insertradially inwardly toward the rearward opening of the needle assembly,and forced through the needle assembly.

[0009] Yet another aspect of the invention relates to an automaticinjection device containing a pre-loaded charge of medicament forautomatically self-administering the medicament upon actuation thereof.The automatic injection device comprises a housing and a medicamentchamber disposed in the housing. The medicament chamber includes a firstcompartment containing a first medicament portion, and a secondcompartment containing a second medicament portion to be mixed with thefirst medicament portion. The device also includes a seal structurebetween the first compartment and the second compartment. The sealstructure is initially in a sealing condition that maintains the firstcompartment separate from the second compartment, and is converted to amixing condition as a result of activation of the device. A needleassembly dispenses the medicament charge from the medicament chamber. Afilter is positioned between the medicament chamber and the needleassembly. The needle assembly comprises a needle and a needle supportfor mounting the needle to the medicament chamber. The needle supportdefines a needle assembly chamber having a rearward opening covered bythe filter. The needle assembly chamber has an inner surface taperingradially inwardly as it extends axially forwardly toward a rearward endof the needle. The device also has an activation assembly carried by thehousing that includes a stored energy source. Activation of theactivation assembly releases the stored energy from the stored energysource, causing the seal structure to be converted from the sealingcondition to the mixing condition, and thereby causing or allowing thefirst and second medicament compounds to be mixed and forced through theneedle assembly.

[0010] A further aspect of the invention relates to a method of fillingan automatic injection device. The method comprises filling a frontcompartment of a chamber within the automatic injection device with adry medicament compound from a front end of the chamber. The method alsocomprises filling a rear compartment of the chamber with a wetmedicament portion from a rear end of the chamber. The rear compartmentis separated from the front compartment by a seal structure. Finally,the method comprises sealing the rear compartment of the chamber,placing a tapered insert in the front end of the chamber, and attachinga needle assembly to the front end of the chamber. The tapered inserthas a tapered flow pathway which is tapered such that the diameterincreases as it extends rearwardly.

[0011] These and other aspects and advantages of the invention will bedescribed below.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The invention will be described in conjunction with the followingdrawing figures, in which like reference numerals designate likeelements, and in which:

[0013]FIG. 1 is a longitudinal cross-sectional view of a wet/dryautomatic injector assembly in accordance with an embodiment of thepresent invention;

[0014] FIGS. 2A-2B illustrate longitudinal cross-sectional views ofneedle support assemblies in accordance with certain embodiments of thepresent invention;

[0015] FIGS. 3A-3D illustrate cross-sectional side views of variouscartridge or chamber configurations and corresponding needle assemblyoptions according to certain embodiments of the present invention;

[0016]FIG. 4 is an enlarged partial cross-sectional side view of aneedle assembly/cartridge engagement according to another embodiment;

[0017] FIGS. 5A-5D illustrate cross-sectional side views of variousembodiments of a seal structure according to the present invention;

[0018]FIG. 6A is a longitudinal cross-sectional side view of a sealstructure in accordance with another embodiment of the presentinvention, wherein the movable sealing plug is in a closed sealingposition blocking the flow of the liquid injection solution;

[0019]FIG. 6B is a longitudinal cross sectional side view of sealstructure similar to 6A, but showing the movable sealing plug in an openby-pass position permitting the flow of the liquid injection solution;

[0020]FIG. 6C is a lateral cross sectional view of the seal structure ofthe present invention taken through the line 6C-6C in FIG. 6A;

[0021]FIG. 6D is a lateral cross sectional view of the seal structure ofthe present invention taken through the line 6D-6D in FIG. 6B;

[0022]FIG. 7 is a longitudinal cross-sectional view of a wet/dryautomatic injector cartridge or chamber configuration in accordance withanother embodiment of the present invention;

[0023]FIGS. 8A and 8B are longitudinal cross sectional views of twoadditional embodiments of seal structures in accordance with the presentinvention;

[0024]FIG. 9 is a longitudinal cross-sectional view of a chamber andneedle assembly according to a further embodiment of the invention;

[0025]FIG. 10 is a perspective view of an outer sealing member in thechamber and needle assembly of FIG. 9;

[0026]FIG. 11 is a front elevational view of the outer sealing member ofFIG. 10;

[0027]FIG. 12 is a longitudinal sectional view of the outer sealingmember of FIG. 10, taken through Line 12-12 of FIG. 11;

[0028]FIG. 13 is a perspective view of a tapered insert in the chamberand needle assembly of FIG. 9;

[0029]FIG. 14 is a front elevational view of the tapered insert of FIG.13;

[0030]FIG. 15 is a longitudinal sectional view of the tapered insert inthe chamber and needle assembly of FIG. 13, taken through Line 15-15 ofFIG. 14;

[0031]FIG. 16 is a longitudinal sectional view of a portion of theneedle assembly of FIG. 9, illustrating a chamber behind the needleassembly filter; and

[0032] FIGS. 17A-17F are sectional and partially sectional views of achamber illustrating a process for filling it with dry and liquidmedicament components.

DETAILED DESCRIPTION

[0033] In the following description, the present invention is describedin connection with a push button type auto injector, whereby the userremoves an end cap assembly and presses a button to trigger theinjection process. The present invention, however, is not limited topush button type automatic injectors; rather, it is contemplated thatthe present invention may be incorporated into a nose activated autoinjector, as described for example in U.S. Pat. No. 5,354,286, thedisclosure of which is hereby incorporated herein by reference for suchteaching.

[0034]FIG. 1 is a longitudinal cross-sectional view of an automaticinjector assembly 10 in accordance with an embodiment of the presentinvention. The automatic injector assembly 10 includes a generallyhollow tubular plastic housing 110. Generally, the housing 110 includesan injection end 111 and an activation end 112, as shown in FIG. 1. Inthe embodiment shown, an actuator assembly 120 is inserted into therearward end of the housing 110. The actuator assembly 120 is receivedwithin the housing 110 until flange 115 of a sleeve member 144 iscaptured within an annular groove 117 on the interior surface of housing110. A removable safety cap 130 is releasably secured to the actuatorassembly 120.

[0035] The actuator assembly 120 may be of any conventional type asknown in the art, such as that disclosed in commonly assigned U.S. Pat.No. 5,391,151 hereby incorporated by reference. The present inventionemploys a rear-end activating device, similar to that in theaforementioned U.S. Pat. No. 5,391,151, and is therefore only brieflydescribed herein. The actuator assembly 120 includes an activationbutton sleeve 132 having internal activation surfaces 134. Theactivation assembly further includes a plastic collet 122 with a splitrearward portion forming spring fingers 136 as known in the art. Thesafety cap 130 has a pin portion 138 that extends between the springfingers 136 so as to keep them spread apart when the injector is in astorage condition. The spring fingers 136 terminate in semi-conicalconfigurations including rearwardly facing sloping surfaces 139 andforwardly facing flat surfaces 142. The collet 122 is surrounded by acylindrical sleeve 144 having inwardly extending flange 146 at therearward end thereof. The collet 122 has a forward annular flange 148. Acoil spring 250 surrounds the collet 122 and is compressed between theflange 148 and flange 146. The collet flat surfaces 142 are retained inengagement with the rearwardly facing surfaces of the flange 146, andthus prevented from moving off of the flange surfaces by the pin 138when the injector is stored.

[0036] To activate the injector, the safety pin 130 is manually pulledoff of the rear end of the injector, thus removing pin 138 from betweenthe fingers 136. The activation button 132 can then be pushed inwardly,and as a result of the activation surfaces thereof, 134 engages thesloping surfaces 139 of the spring fingers 136. This forces the springfingers 136 inwards toward one another and off of the retaining surfacesof the flange 146. The compressed spring 250 is then free to release thestored energy therein to move the collet 122 forwardly under the forceof the spring to affect an injection operation as will be describedlater in more detail.

[0037] The actuator assembly 120 may be of any type known in theautomatic injector art that employs releasable stored energy. Forexample, rather than employing a spring, it may employ a charge ofcompressed gas.

[0038] Located within the interior of the housing 110 is a vial orchamber 150, preferably made of glass, for containing both a liquidinjection solution and a dry medicament, or other types of medicamentportions, as appropriate. The chamber 150 is preferably a hollowcylinder, with a smooth cylindrical inner surface. The liquid injectionsolution is located within a wet portion or compartment 151 of thechamber 150. The dry medicament is located within a dry portion 152 orcompartment of the chamber 150. It is contemplated that the drymedicament may be in powder, lyophilized, freeze-dried, or any othersolid formulation known in the art. A seal structure 160 engages theinterior side walls of the chamber 150 to seal the dry portion 152 fromthe wet portion 151 and to prevent seepage of the liquid injectionsolution into the dry portion 152 prior to activation of the injectorassembly. Further, a needle assembly 140 mounts to the forward end ofvial or chamber 150 to inject the medicament upon activation of theinjector assembly. In this embodiment, the forward end portion of thechamber 150 has an annular groove 153 formed therein for attachment ofthe needle assembly 140. The needle assembly 140 includes afunnel-shaped needle support 143. The wide end of the needle support 143has an annular rib 145 that is snap-fit into groove 153 to form a sealwith the chamber 150. The needle support 143 can be made of a resilientplastic material, or metal with a rubber seal that seats into groove153. The forward narrow end 147 (see FIG. 2A) of the needle support 143sealingly receives the rearward end of hollow needle 141. The needlesupport 143 forms a sealed fluid channel from the chamber 150 to theneedle 141. A rubber needle sheath 202 surrounds the needle 141 andreceives the narrow end 147 of the needle support 143. A filter 190 issealingly retained across the entire wide-end mouth of the needlesupport 143 by an annular sealing washer 156. Alternatively, the filter190 could be ultrasonically welded or otherwise secured to the needlesupport 143.

[0039]FIGS. 2B, 3A, and 4 illustrate another embodiment of a needleassembly 140 and chamber 150. The chamber 150 in this embodiment isknown in the art as a dental cartridge. The dental cartridge has acylindrical rear portion and a narrowed forward neck portion defining anouter annular groove 153. The forward end of the dental cartridgedefines an annular flange portion 154. In this embodiment, the needlesupport 143 has a rearward annular flange 155 that receives an annularsealing member 156 that surrounds both sides of flange 155. The sealingmember 156 serves to seal a filter 190 over the wide end of the funnelshaped needle support 143. The rearward surface of the sealing member156 is sealingly clamped against the forward surface of chamber flange154 by a metal retaining clamp 157 as best seen in FIG. 4.

[0040] As shown in FIG. 1, forward end 1221 of the collet 122 extendsinto the rearward end of chamber 150 and is adapted to connect with aplunger 170 rearwardly sealing the wet container 151. The plunger 170 isadapted to sealingly engage the side wall of the wet container 150 toprevent leakage of the contents (e.g., liquid injection solution) of thewet container 151. The plunger 170 is preferably formed from a materialhaving low frictional properties such that the collet 122 and plunger170 may easily slide within the wet container 150 when operated.Alternatively, the plunger 170 may be lubricated with silicone or othersuitable non-reactive lubricant. The movement of the collet 122 and theplunger 170 pressurizes the liquid located within the wet container 151.A suitable medicament is located within a dry container 152.

[0041] The embodiment of FIGS. 1 and 2A is advantageous in that it hasan open mouth configuration wherein the needle-end of the vial orchamber is not significantly narrowed or tapered. Such an open mouthconfiguration permits direct access to the dry portion 152 of chamber150 for easy loading. Further, the open mouth configuration aids inpreventing cross contamination between wet portion 151 and dry portion152 in that the dry portion 152 does not have to be filled throughliquid portion 151 of chamber 150. Needle assembly 140 can be mounted tovial or chamber 150 in a snap-on configuration (FIG. 3B), an internalmount configuration (FIG. 3C), or an external needle assemblyconfiguration (FIG. 3D).

[0042] As mentioned above, the seal structure 160 is adapted to engagethe interior side walls of chamber 150 to prevent passage of thecontents (e.g., liquid injection solution) of wet portion 151 into thedry portion 152 prior to activation of the automatic injection assembly.Generally, seal structure 160 can include an outer sealing member 180, amovable sealing plug 166, a by-pass zone 165, at least one flow path167, and preferably also includes a filter or membrane 164. Withreference to FIGS. 5A-D, seal structure 160 can preferably be formed asa six piece (FIG. 5A), five piece (FIG. 5B), four piece (FIG. 5C), orthree piece (FIG. 5D) configuration.

[0043] More particularly, with reference to FIG. 5A, the outer sealingstructure 180 of the six piece configuration can comprise a two pieceannular rigid body 181 wherein members 181 a, 181 b thereof are formedinto the two piece rigid body using, e.g., annular weld connections orother bonding techniques known in the art. Outer sealing structure 180can further include multiple external sealing members 182, e.g., twoO-rings, to provide an annular sealing engagement with the inner wall ofvial or compartment 150. The sealing structure 180 further includes aninternal plug member 166 and a filter or dispersion membrane 164 as willbe discussed in greater detail later.

[0044] In another embodiment, as shown in FIG. 5B, rather than pluralO-rings, outer sealing structure 180 can include a single externalsealing member 182, e.g., a unitary gasket, to provide an annularsealing engagement with the inner wall of vial or compartment 150.External sealing member 182 may optionally be secured to two piece rigidbody 181 using any bonding techniques known in the art. Further, rigidbody members 181 a, 181 b may be shaped such that they securingly engageexternal sealing members 182 within notched recesses 183. Alternately,sealing members 182 may be secured to rigid body members 181 a, 181 b byan interference fit. As with the first embodiment, a filter or membrane164 is clamped in place at the proximal end of flow path 167 betweenmember 181 a and member 181 b of the two piece rigid body.

[0045] In another embodiment, as shown in FIG. 5C, outer sealingstructure 180 comprises a unitary internal rigid member 181 and anexternal sealing member 182. Again, internal rigid member 181 andexternal sealing member 182 may optionally be secured together using anybonding techniques known in the art. Further, internal rigid member 181and external sealing member 182 may be formed such that they securinglyengage each other using a combination of notched recesses 183 andextending shoulders 184. The filter or membrane 164 can be held in placebetween internal rigid member 181 and shoulder 184 of external sealingmember 182. Alternatively, the filter 164 may be ultrasonically weldedor otherwise secured to the rigid member 181. In yet another embodiment,as shown in FIG. 5D, outer sealing object 180 can comprise a unitaryexternal sealing member 182 which can optionally be molded so as toaccommodate filter or member 164 within retaining recess 185. FIGS. 6Aand 6B illustrate another embodiment that is very similar to that ofFIG. 5A, but provides a slightly different shape for outer annular rigidbody 181 and particularly the members 181a, 181 b thereof.

[0046] In each embodiment illustrated in FIGS. 5A-5D and 6A-6B, externalsealing member 182 is preferably formed from a non-reactive elastomermaterial which can provide for the necessary sealing engagement with theinner wall of vial or compartment 150. Further, external sealing member182 can optionally be lubricated with silicon or other suitablenon-reaction lubricant to facilitate movement of the outer sealingobject 180 forwardly within vial or compartment 150 upon receivingsufficient force as will be described. The movable sealing plug 166 ispreferably formed from a material, such as an elastomer or PTFE, havinglow frictional properties such that the sealing plug 166 may easilyslide within outer sealing object 180 when the injector is activated.The movable sealing plug 166 may also optionally be lubricated withsilicon or other suitable non-reactive lubricant. In the embodimentsillustrated, and as specifically shown in FIG. 6B, it is preferred thatthe outer annular structure 180 defines an inner surface having a smoothcylindrical configuration towards the rearward portion 169 thereof, andlongitudinally extending grooves 168 towards the forward portionthereof. The grooves 168 create a flowpath or flowpaths 167 throughwhich liquid in the wet compartment 151 can bypass seal plug 166 whenthe plug 166 is moved forwardly from sealing engagement with cylindricalsurface portion 169 into the grooved portion 168. The movement of thesealing plug 166 into the by-pass area 165 opens the fluid flow path 167between wet portion 151 and dry portion 152. The movable sealing plug166 preferably includes a plurality of circumferential grooves 186 toprovide for enhanced sealing engagement and to facilitate sliding actionof the plug 166.

[0047] As mentioned above, the seal structure 160 preferably includesfilter or membrane 164 at the end of flow path 167 through which theliquid injection solution may pass after the injector has beenactivated. The liquid injection solution then enters the dry portion 152of the chamber 150 where it mixes with and dissolves the dry medicament.More particularly, the filter 164 disperses the liquid injectionsolution exiting the seal structure 160 to present laminar fluid flow tothe full surface of the dry medicament, thereby wetting the entiresurface of the dry medicament for rapid and complete dissolution. Thefilter membrane 164 can be any structure that generally uniformlydistributes the liquid across the entire diameter of the chamber 150 forenhanced dissolution of the dry medicament.

[0048] During operation, manual activation of the actuator assembly 120releases the collet 122 (as described above), which applies pressure onthe plunger assembly 170. The application of pressure on the plungerassembly 170 by the collet and spring assembly 124 moves the plunger 170in the direction of the needle assembly 140. As a result, the entirechamber 150 and needle assembly 140 are moved forwardly in the housing110 such that needle 141 pierces through the front end of sheath 202 andexits through the forward end of the housing 110, and particularlythrough a hole 204 in the front nose-cone portion 206 of the housing.The sheath 202, which serves to maintain the needle 141 sterile when theinjector is in storage, also serves as a shock absorber duringactivation as it is compressed in generally accordion like fashionbetween the nose cone 206 and needle support 143.

[0049] When the needle 141 is extended from the housing 110 and thechamber 150 and needle support 143 approach the nose cone 206 portion ofthe housing so that further forward movement of chamber 150 issubstantially resisted, the plunger 170 then begins to travel forwardlythrough the chamber 150. This pressurizes the liquid injection solutionlocated within the wet compartment 151. With reference to FIGS. 6A-6B,the increased pressure within the wet compartment 151 moves the sealingplug 166 from a first sealed position wherein sealing plug 166 issealingly engaged with surface 169 of outer sealing structure 180 (FIG.6A) to a second by-pass position (FIG. 6B) that allows the injectionsolution to flow through flow path 167 created by grooves 168 andthereby through seal structure 160.

[0050] As described above, the high pressure developed within the wetportion 151 in response to movement of the collet 122 and the plungerassembly 170 forces the liquid injection solution through the sealstructure 160 dissolving the drug into a medicament injection solutionwhich will then be forced out through the needle 141 and into thepatient. As the collet 122 and plunger assembly 170 continue forward,the plunger 170 will eventually contact the seal structure 160, which,in a preferred embodiment, causes the seal structure 160 to move in thedirection of the needle assembly 140. Movement of the seal structure 160would cause any remaining solution within the portion 152 to bedispersed through the needle assembly 140, so as to reduce the amount ofresidual medicament remaining within the chamber 150.

[0051] As shown in FIGS. 2A, 2B and 4, a membrane or filter 190 ispreferably provided adjacent the needle assembly 140 to prevent any drymedicament particles from clogging the rearward end of needle 141 priorto an injection operation. The membrane 190 may also serve to slightlyrestrict or slow injection of medicament into the patient, to facilitatemore thorough dissolution during injection.

[0052] More particularly, to prevent the passage of undissolved drymedicament to the needle assembly 140, a medicament support 190 ispreferably provided between the end of the dry compartment 152 and theneedle assembly 140. The support 190 can serve to prevent blockage ofthe needle assembly 141 by preventing the dry medicament from enteringthe area surrounding the needle assembly 140 while permitting passage ofthe mixture of dissolved medicament and liquid injection solution. Thesupport 190 may be configured as described in U.S. ProvisionalApplication No. 60/238,448, which is herein incorporated by reference ina manner consistent with this disclosure. It is contemplated thatmultiple supports 190 may be located within the dry compartment 152. Theprovision of the supports 190 may also improve the laminar flow of theliquid injection solution through the dry medicament thereby improvingdissolution.

[0053] Further, a diaphragm assembly (not shown) may also be providedadjacent the medicament support 190, as known in the art. The diaphragmassembly acts to prevent the passage of the liquid injection solution tothe needle assembly 140 prior to activation of the actuator assembly120. More particularly, the diaphragm assembly will not rupture untileither the butt end of the needle assembly 140 ruptures the expandeddiaphragm or sufficient pressure builds in the dry compartment 160 torupture the diaphragm, again as known in the art.

[0054] As described above, the movement of the collet 122 causes theinjection needle 141 of the injection assembly 140 to advance andprotrude through the housing 110. As such, the injection of themedicament can be performed with a simple operation. In sum, the usersimply removes the end cap assembly 130, locates the injection end ofthe housing 110 adjacent the injection site, and presses the push button132. This operation automatically triggers the operation of the driveassembly or spring 250 to advance the collet 122 causing the liquidinjection solution located within the wet portion 151 to enter the dryportion 152 through the seal structure 160. The dissolved medicament isthen transmitted through the injection needle 141 to provide the userwith the necessary dose of medicament. The automatic injector 10 inaccordance with the present invention reduces the amount of timerequired to administer medicament compared to other wet/dry injectorsand eliminates the need for mixing by the user.

[0055] The seal structure 160 advantageously enables the manufacture ofa superior wet/dry auto injector with a complementary combination ofcomponents that are either known in the art of conventionalauto-injectors or are otherwise relatively simple to manufacture. Theseal structure 160 enables sufficient mixing of wet and dry medicamentcomponents without requiring manual shaking. This mixing action isenhanced by the filter or membrane 164. In a preferred embodiment, thefilter 164 is a supported, hydrophobic acrylic copolymer cast on anon-woven nylon support. Preferably, it is a FlouRepel treated membranefor superior oleophobicity/hydro-phobicity.

[0056] In another embodiment, shown in FIG. 7, the automatic injectorcartridge includes a needle assembly 140 located within the dry portion152. The needle assembly 140 extends within the dry portion 152 to thesealing structure 180, described above in connection with FIGS. 5A-5D.The sealing structure 180 separates the dry portion 152 from the wetportion 151. As shown in FIG. 7, the cartridge further includes aplunger 170 positioned therein. The plunger 170 is configured to engagethe collet 122 of the activation assembly 120. The cartridge includes asheath 301. Like the sheath 202, the sheath 301 maintains the needle 141in a sterile environment until it projects from the end of the sheath301 in response to activation of the activation assembly 120. Duringoperation, the needle assembly 140 passes through the dry portion 152 asthe wet medicament passes through the sealing structure 180.

[0057] In other embodiments (see FIGS. 8A and 8B), no inner plug 166 isprovided. Rather, the outer structure 180 is simply complemented by aseal membrane 226 that extends across the inner area defined by theinner surface of the outer structure. When the chamber 150 reaches theforward end of the housing during an injection operation, pressurizationof the wet compartment 151 causes the seal membrane 226 to rupture,thereby allowing the seal structure 160 to permit liquid to passtherethrough. In this embodiment, it may be desirable to provide theseal structure 160 with a pointed member 228 disposed adjacent to theseal membrane 226 to facilitate rupturing of the seal membrane uponpressurized expansion thereof during an injection operation. The member232 on which the pointed member 228 is mounted has a plurality ofpassages 234 that permits fluid to pass therethrough. Filter or membrane164 is preferably mounted distal to the passages 234 to present laminaror distributed flow to the dry medicament.

EXAMPLES

[0058] An injector according to the present invention was loaded withliquid injection solution and dry medicament and activated with thefollow results. Loaded Dispensed Dry Dry Operational Powder Fluid PowderFluid Time Mg Ml % mg ml Secs. 531 2.7 94 497 2.3 4.0 557 2.7 93 515 2.34.5 582 2.6 92 537 2.2 4.4

[0059] Other embodiments and modifications of the invention are alsocontemplated. For example, a cover assembly, described for example inU.S. Pat. No. 5,295,965 (the disclosure of which is specificallyincorporated herein by reference) may be secured to the injection end ofthe housing 110 after deployment of the medicament. Furthermore, theautomatic injector may further include a nipple plunger assembly, asdescribed for example in U.S. Pat. No. 5,713,866 (the disclosure ofwhich is specifically incorporated herein by reference).

[0060] In yet a further embodiment, the forward dry chamber 152 containsthe needle 141, as shown in FIG. 7. The needle 141 is forced through aforward plug stopper upon initial compression of the two chamber system.As known in the art, providing the needle 141 in the forward chamber 152provides improved longitudinal compactness of the design.

[0061] In yet another embodiment, a pre-filled syringe is provided withthe seal structure disposed between wet and dry components.

[0062] In further contemplated embodiments, the seal structure 160 canbe used in the same type of injector described herein, except ratherthan employing a dry (powder) medicament separated by a liquidcomponent, a first liquid medicament is separated from a second fluidcomponent by the seal structure 160. In yet another embodiment, the sealstructure 160 can be used in what is known in the art as a “needlelessinjector” where an injection can be made into a patient without a needleor cannula.

[0063]FIG. 9 is a longitudinal cross-sectional view of a chamber 350mounted to a needle assembly 340 according to a further embodiment ofthe invention. Neither a housing 110 nor an actuator assembly 120 isshown in FIG. 9; however, the chamber 350 and needle assembly 340 may beused with the housings 110 and actuator assemblies 120 described aboveor with substantially any known housing or actuator assembly.

[0064] In the chamber 350 and needle assembly 340 shown in FIG. 9, manyof the components are the same as those described above with respect toFIG. 1; therefore, the description above will suffice for thosecomponents.

[0065] Like the chamber 150, the chamber 350 has a wet portion orcompartment 151 and a dry portion or compartment 152. A sealingstructure 360 separates the wet portion 151 and the dry portion 152. Thesealing structure 360 includes an outer sealing member 380, a moveablesealing plug 166, a by-pass zone 165, and may also include a filter ordispersion membrane 164. Although a moveable sealing plug 166 is shownin FIG. 9, the sealing structure 360 may include a rupturable sealmembrane 226 instead of a sealing plug 166, as shown in FIGS. 8A and 8B.

[0066]FIG. 10 is a perspective view of the outer sealing member 380.FIG. 11 is a front elevational view of the sealing member 380, and FIG.12 is a sectional view of the outer sealing member 380 taken throughLine 12-12 of FIG. 11. As shown, the outer sealing member 380 has anannular wiper portion 382 that makes sealing contact with the inner wallof the dry portion 152 of the chamber 350 and extends axially forwardly,in the direction of actuating movement along the longitudinal axis ofthe chamber 350, toward the needle assembly 140.

[0067] While the outer sealing members 180 that were described above doform a seal with the inner wall of the container 150, during theactuation process, powder from the dry medicament in the dry portion 152tends to accumulate around the sealing member 180, 380 at theseal/container interface. As the device actuates, some of the powderthat accumulates around the sealing member 180, 380 can be driven orforced into the space between the glass and the sealing member 180. Theentire area around and between the sealing member 180 and the inner wallof the container 150 can become a “dead space,” in which accumulatedpowder cannot properly mix with fluid.

[0068] The wiper portion 382 helps to eliminate the accumulation ofpowder around the sealing member 380 by “wiping” or “scraping” anyaccumulated powder away from the wall of the chamber 350 and directingit radially inwardly, where it can properly mix with the wet medicamentportion as the sealing member 380 passes through the dry portion 152. Asshown in FIG. 9, the wiper portion 382 makes contact with the inner wallof the dry portion 152 of the chamber 350 along substantially theentirety of its length. The extent of contact between the wiper portion382 and the inner wall of the dry portion 152 is possible, at least inpart, because the wiper portion 382 extends axially. Although it wouldbe possible to construct a wiping structure that extended radially orangularly outward from the main body of the sealing member 380, such awiping structure would not be in contact with the inner wall of the dryportion 152 over substantially the entirety of its length. Therefore, itwould be possible for such a putative wiping structure to cause anundesirable accumulation of medicament powder, particularly ifmedicament powder were to move past it and into the space between it andthe inner wall of the dry portion 152. Accordingly, the straight,forwardly-extending wiper portion 382 is currently preferred.

[0069] A wiper portion 382, although shown in the embodiment of FIG. 9,may be used in any of the embodiments shown and described above and inany variations thereof.

[0070] As shown in FIG. 9, the chamber 350 has an “open mouth”configuration; i.e., the container itself does not taper substantiallyas it meets the needle assembly 340 (for example, as compared with theembodiment shown in FIG. 3A). The advantages of having an “open mouth”container were described above with respect to the container 150. If the“mouth” of the container (i.e., the opening into the dry portion 152 ofthe container) is open and wide, it becomes easier to load the drycomponent of the medicament. However, having a tapered portion adjacentto the needle assembly 340 helps to direct the medicament radiallyinwardly, toward the needle assembly 340, when the injection is takingplace.

[0071] In order to realize the advantages of an “open mouth” containerand the advantages of a tapered container, the chamber 350 includes atapered insert 384 at its mouth, just behind the needle assembly 340.FIG. 13 is a perspective view of the tapered insert 384, FIG. 14 is afront elevational view, and FIG. 15 is a sectional view through Line15-15 of FIG. 14.

[0072] The tapered insert 384 tapers radially inwardly as it extendsaxially forwardly, such that it forms a funnel portion 386 with a smallcentral opening 388 at one end. The tapered insert 384 also has arearward open end 389 with a larger open diameter. The insert 384sealingly engages the walls of the chamber 350. Extending radiallyoutward from the outer surface of the funnel portion 386 proximate tothe small central opening 388 is an annular sealing flange 390. In theembodiment shown in FIGS. 13-15, the annular sealing flange 390 is anintegral portion of the tapered insert 384. However, in someembodiments, the annular sealing flange 390 may be joined to the funnelportion 386 by adhesives or other securing methods. Additionally, aswill be described in more detail below, in some configurations, theannular sealing flange 390 may be absent. The insert 384 is preferablyformed from a material that will not react with the dry medicamentstored in the compartment 152.

[0073] The chamber 350 and needle assembly 340 include a metallic skirt,generally indicated at 392, that is rolled or crimped so as to captureor secure the needle assembly 340 to the front end of the chamber 350.In this embodiment, the annular sealing flange 390 fits between thechamber 350 and needle assembly 340 so as to form a seal between them.Either the annular sealing flange 390 itself or, depending on theconfiguration, the entire tapered insert 384 may be made of anelastomeric or other rubber material suitable for sealing.

[0074] The tapered insert 384 may be removed from the chamber 350 inorder to effect the loading of the dry medicament and then inserted intothe chamber 350 prior to joining with the needle assembly 340. Althoughthe tapered insert 384 is shown with a funnel portion 386 of constant,radially inward taper, the tapering of the tapered insert 384 may be ofany type that will facilitate fluid flow from the chamber 350 into theneedle assembly 340.

[0075] At the forward end of the tapered insert 384, the small, centralopening 388 in the insert 384 is covered by a filter 190 that ispositioned between the tapered insert 384 and the needle support 343 tofilter fluids passing from the chamber 350 into the needle assembly 340,so as to prevent any undissolved medicament from entering the needleassembly 340. Forward of the filter 190, defined by the rearward(container-facing) side of the needle support 343 is a chamber 394 thattapers radially inwardly toward its forward end. The chamber 394 iscontoured to expose a substantial portion of the surface area of thefilter 190 to the flow between the chamber 350 and the needle assembly340. Preferably, the chamber 394 has an opening at least as large as thesmall central opening 388 in the tapered insert 384. In the embodimentshown in FIG. 9, the chamber 394 is substantially hemispherical,although other configurations may be used. The chamber 394 can be seenmore clearly in FIG. 16, which is a longitudinal cross-sectional view ofa portion of the needle assembly 340. The chamber 394 allows greater,more laminar, and more fully developed flow through the filter 190 tothe needle 141. Furthermore, the chamber 394 is shaped to direct theflow of medicament to the needle 141.

[0076] As is also shown in FIG. 16, neither the needle 141 nor any otherstructure protrudes into the chamber 394. Although it would be possibleto construct a chamber 394 and needle assembly such that a portion ofthe end of the needle protruded into the chamber 394, such anarrangement might cause turbulent flow around the end of the needle thatprotruded into the chamber 394, or might otherwise eliminate some of thebenefits of the chamber 394.

[0077] The sealing member 380 with wiper portion 382, tapered insert384, and chamber 394 may all be used in a wet/wet autoinjector assemblythat includes two fluid medicament components. In a wet/wet autoinjectorassembly, a burstable membrane is typically positioned over the openingof the compartment adjacent to the needle assembly, in order to preventfluid in that compartment from leaking out of the compartment and intothe needle assembly. If the sealing member 380, tapered insert 384, andchamber 394 are provided in a wet/wet autoinjector assembly, a burstablemembrane may be provided as a portion of the tapered insert 384. Forexample, the burstable membrane could be positioned in the funnelportion 386 of the insert.

[0078] The sealing member 380, tapered insert 384, and chamber 394 mayalso be used in a wet/dry or wet/wet autoinjector assembly that does notinclude all of the features described above. For example, the taperedinsert 384 and chamber 394 may be used in any wet/dry or wet/wetautoinjector in order to improve the loading and dispensing performanceof the autoinjector.

[0079] A chamber for an autoinjector may be filled with appropriatemedicament components in several different ways. For example, one commonway to fill an autoinjector chamber is to fill a first medicament (e.g.,a wet medicament) through an opening in the chamber and then fill asecond medicament (e.g., a dry medicament) through that same opening inthe chamber. This process, while common, tends to causecross-contamination because both wet and dry medicaments are filledthrough the same opening. For example, if a dry powder medicament isfilled first, any powder that accumulates around the opening may mixwith a subsequently-filled wet medicament, thereby contaminating thecontents of the wet compartment. Conversely, if the wet medicament isfilled first, liquid that accumulates around the opening may mix withsome of the subsequently-filled dry medicament, thereby contaminatingthe contents of the dry compartment.

[0080] However, using a chamber 150, 350 according to the invention, itis advantageous to fill the chamber 150, 350 using a separate opening inthe chamber 150, 350 for each type of medicament, thus eliminating thecross-contamination problem. This sort of filling process for a chamber150, 350 includes a number of tasks and will be described below withrespect to the chamber 350, although the described process is, ingeneral, equally applicable to the other embodiments described above.Ordinarily, the filling process would be performed in an asepticenvironment.

[0081] Typically, the chamber 350 is initially open at both ends anddoes not include any interior structures, as shown in FIG. 17A. A sealstructure, such as seal structure 360, is first inserted into thechamber 350 so that it is positioned substantially as shown in FIG. 17B.

[0082] Once the seal structure 360 is in place, the chamber 350 isremoved to or placed in a low particulate aseptic environment, and ispositioned so that the wet portion or compartment 151 can be filledthrough an opening 396 in the rear end of the chamber 350, as shown inFIG. 17C. (The low particulate environment prevents possiblecross-contamination of the wet portion 151.) After the wet portion 151is filled, the opening 396 in the rear end of the chamber 350 is sealedby installing the plunger 170, as shown in FIG. 17D. The placement ofthe chamber 350 in a low particulate environment prior to filling thewet portion 151 helps to prevent contamination of the wet portion 151 bypowder or other particulates.

[0083] Once the wet portion 151 is filled with the desired liquidmedicament portion and the rear end is sealed with the plunger 170, thechamber 350 is removed from the low particulate environment and isplaced in an appropriate aseptic environment so that the dry portion orchamber 152 of the chamber 350 can be filled through an opening 398 inthe front of the chamber 350. There are two common ways of filling thedry portion 152. One way to fill the dry portion 152 is to place a drypowder directly into the dry portion 152 through the opening 398, asshown in FIG. 17E.

[0084] Another way to fill the dry portion 152 is to fill the dryportion 152 with a liquid medicament through the opening 398 and thenlyophilize the liquid medicament directly in the dry portion 152 toleave only the desired dry medicament. While this process of liquidfilling and lyophilizing may be used, it sometimes leaves residues inthe dry portion 152, which may interfere with the stability of the drymedicament or otherwise contaminate it.

[0085] A third way to fill the dry portion 152 is to lyophilize a liquidmedicament in a separate container to form a lyophilized dry medicamenttablet 400 and then deposit the dry medicament tablet 400 in the dryportion 152 through the opening 398, as shown in FIG. 17F. Thisvariation of the filling process is used most advantageously with achamber that has a relatively wide opening into its dry portion, so thattablets of various sizes can be accommodated. If a chamber has arelatively narrow opening into its dry portion, it may be necessary tofill that dry portion with powder, or to lyophilize a liquid medicamentdirectly in the dry portion to form a dry powder.

[0086] After the dry portion 152 is filled, a tapered insert 384 isplaced in opening 398 of the chamber 350 and the needle assembly 340 issecured over the tapered insert 384. When the process is complete, thechamber 350 is as shown in FIG. 9.

[0087] Although the present invention has been described with respect toa number of embodiments, those embodiments are meant to be illustrative,rather than limiting. As those of ordinary skill in the art willunderstand, modifications and variations are possible within the scopeof the appended claims.

What is claimed is:
 1. An automatic injection device containing apre-loaded charge of medicament for automatically self-administering themedicament upon actuation thereof, the device comprising: a housing; amedicament chamber disposed in the housing, the medicament chamberincluding a first compartment containing a dry medicament portion, and asecond compartment containing a wet medicament portion to be mixed withthe dry medicament portion; a seal structure between the firstcompartment and the second compartment, the seal structure beinginitially in a sealing condition that maintains the first compartmentseparate from the second compartment, the seal structure including: atleast one flow path formed therein, and an annular wiper portiondisposed at the front end of the seal structure and positioned tomovingly engage inner walls of the first compartment as the sealstructure is moved through said first compartment, said wiper portionbeing configured to direct dry medicament particles engaged with theinner walls radially inwardly as the seal structure moves through thefirst compartment, the seal structure being converted to a mixingcondition as a result of activation of the device; a needle assemblythat dispenses the mixed medicament portions from the medicamentchamber; and an activation assembly carried by the housing and includinga stored energy source, wherein activation of the activation assemblyreleases the stored energy from the stored energy source, causing theseal structure to be converted from the sealing condition to the mixingcondition, and thereby causing or allowing the medicament portions to bemixed and forced through the needle assembly.
 2. The automatic injectiondevice of claim 1, wherein the first compartment is adjacent the needleassembly and disposed forwardly of the second compartment.
 3. Theautomatic injection device of claim 1, further comprising an insertmounted in the forward end of the chamber adjacent the needle assembly,the insert defining a tapering flow pathway that tapers radiallyinwardly as it extends axially forwardly.
 4. The automatic injectiondevice of claim 3, further comprising a filter positioned between themedicament chamber and the needle assembly.
 5. The automatic injectiondevice of claim 4, wherein the needle assembly comprises a needlesupport for mounting the needle assembly to a front end of themedicament chamber, the needle support defining a chamber providedadjacent to the filter on a needle assembly side of the filter.
 6. Theautomatic injection device of claim 5, wherein the needle supportchamber adjacent to the filter has an enlarged rearward end opening of asize that is at least as large as a front end opening of the insert. 7.The automatic injection device of claim 6, wherein the needle supportchamber adjacent to the filter has a substantially hemispherical shape.8. The automatic injection device of claim 7, further comprising a fluiddistributing member disposed between the first compartment and thesecond compartment.
 9. The automatic injection device of claim 8,wherein the fluid distributing member is a filter.
 10. The automaticinjection device of claim 1, wherein the seal structure comprises anouter seal structure carrying the wiper portion, the flow path beingformed in the outer seal structure, and a plug member for sealing theflow path when the seal structure is in the sealing condition.
 11. Theautomatic injection device of claim 10, wherein the seal structure hasan outer periphery that forms a peripheral seal with an interior wall ofthe medicament chamber, and wherein said plug member is spaced radiallyinward from the peripheral seal that seals the at least one flow pathformed in the seal structure.
 12. The automatic injection device ofclaim 1, wherein the wiper portion comprises a peripheral lip having aninner surface that extends radially inwardly as it extends axiallyrearwardly.
 13. An automatic injection device containing a pre-loadedcharge of medicament for automatically self-administering the medicamentupon actuation thereof, the device comprising: a housing; a medicamentchamber disposed in the housing, the medicament chamber including afirst compartment containing a first medicament portion, and a secondcompartment containing a second medicament portion to be mixed with thefirst medicament portion; a seal structure between the first compartmentand the second compartment, the seal structure being initially in asealing condition that maintains the first compartment separate from thesecond compartment, the seal structure being converted to a mixingcondition as a result of activation of the device; a needle assemblythat dispenses the medicament charge from the medicament chamber, theneedle assembly having a rearward opening with a diameter that is lessthan a diameter of the medicament chamber; an insert mounted in aforward end of the medicament chamber adjacent the needle assembly, theinsert defining a tapering flow pathway that tapers radially inwardly asit extends axially forwardly; an activation assembly carried by thehousing and including a stored energy source, wherein activation of theactivation assembly releases the stored energy from the stored energysource, causing the seal structure to be converted from the sealingcondition to the mixing condition, and thereby causing or allowing thefirst and second medicament portions to be mixed, directed by the insertradially inwardly toward the rearward opening in the needle assembly,and forced through the needle assembly.
 14. The automatic injectiondevice of claim 13, further comprising a filter positioned between themedicament chamber and the needle assembly.
 15. The automatic injectiondevice of claim 14, wherein the needle assembly comprises a needlesupport for mounting the needle assembly to a front end of themedicament chamber, the needle support defining a chamber providedadjacent to the filter on a needle assembly side of the filter.
 16. Theautomatic injection device of claim 15, wherein the rearward opening ofthe needle assembly comprises a rearward end opening in the needlesupport chamber adjacent to the filter, the rearward end opening havinga size that is at least as large as a front end opening of the insert.17. The automatic injection device of claim 16, further comprising afluid distributing member carried by the seal structure.
 18. Theautomatic injection device of claim 13, wherein the seal structurecomprises an outer seal structure carrying a wiper portion, a flow pathformed in the outer seal structure, and a plug member for sealing theflow path when the seal structure is in the sealing condition.
 19. Theautomatic injection device of claim 18, wherein the seal structure hasan outer periphery that forms a peripheral seal with an interior wall ofthe interior chamber, and wherein said plug member is spaced radiallyinward from the peripheral seal that seals the at least one flow pathformed in the seal structure.
 20. The automatic injection device ofclaim 19, wherein the wiper portion comprises a peripheral lip having aninner surface that extends radially inwardly as it extends axiallyrearwardly.
 21. An automatic injection device containing a pre-loadedcharge of medicament for automatically self-administering the medicamentupon actuation thereof, the device comprising: a housing; a medicamentchamber disposed in the housing, the medicament chamber including afirst compartment containing a first medicament portion, and a secondcompartment containing a second medicament portion to be mixed with thefirst medicament portion; a seal structure between the first compartmentand the second compartment, the seal structure being initially in asealing condition that maintains the first compartment separate from thesecond compartment, the seal structure being converted to a mixingcondition as a result of activation of the device; a needle assemblythat dispenses the medicament charge from the medicament chamber; afilter positioned between the medicament chamber and the needleassembly; and an activation assembly carried by the housing andincluding a stored energy source, wherein activation of the activationassembly releases the stored energy from the stored energy source,causing the seal structure to be converted from the sealing condition tothe mixing condition, and thereby causing or allowing the first andsecond medicament compounds to be mixed and forced through the needleassembly; wherein the needle assembly comprises a needle and a needlesupport for mounting the needle to the medicament chamber, the needlesupport defining a needle assembly chamber having a rearward openingcovered by the filter, the needle assembly chamber having an innersurface tapering radially inwardly as it extends axially forwardlytoward a rearward end of the needle.
 22. The automatic injection deviceof claim 21, wherein no rearward portion of the needle protrudes intothe needle assembly chamber.
 23. The automatic injection device of claim22, wherein the needle assembly chamber has a substantiallyhemispherical shape.
 24. The automatic injection device of claim 23,further comprising an insert mounted in the forward end of the chamberadjacent the needle assembly, the insert defining a tapering flowpathway that tapers radially inwardly as it extends axially forwardly.25. The automatic injection device of claim 24, further comprising afluid distributing member carried by the seal structure.
 26. Theautomatic injection device of claim 21, wherein the seal structurecomprises an outer seal structure carrying a wiper portion, a flow pathformed in the outer seal structure, and a plug member for sealing theflow path when the seal structure is in the sealing condition.
 27. Theautomatic injection device of claim 26, wherein the seal structure hasan outer periphery that forms a peripheral seal with an interior wall ofthe medicament chamber, and wherein said plug member is spaced radiallyinward from the peripheral seal that seals the at least one flow pathformed in the seal structure.
 28. The automatic injection device ofclaim 27, wherein the first medicament portion comprises a drymedicament portion and the wiper portion carried by the outer sealstructure is configured to direct dry medicament particles engaged withthe walls of the medicament chamber radially inwardly as the sealstructure is moved through the first compartment.
 29. A method ofproviding a medicament containing chamber of an automatic injectiondevice, comprising: inserting a seal structure into the chamber todivide the chamber into a front compartment and a rear compartment;filling the rear compartment of the chamber with a wet medicamentportion through a rear end of the chamber; sealing the rear end of therear compartment of the chamber; filling the front compartment of thechamber with a dry medicament portion through a front end of thechamber; and sealing the front end of the front compartment of thechamber.
 30. The method of claim 29, wherein sealing the front end ofthe front compartment comprises placing a tapered insert in the frontend of the chamber, the tapered insert having a tapered flow pathwaytherein, the flow pathway being tapered so that the diameter thereofincreases as it extends rearwardly.
 31. The method of claim 30, furthercomprising attaching a needle assembly to the front end.
 32. The methodof claim 29, wherein the rear compartment of the chamber is filled withthe wet medicament portion before the front compartment of the chamberis filled with the dry medicament portion.
 33. The method of claim 32,wherein the seal structure is inserted before the rear compartment isfilled with the wet medicament portion.
 34. The method of claim 29,wherein the dry medicament portion is a powder.
 35. The method of claim29, wherein the dry medicament portion is a tablet sized and adapted tofit through the front end of the chamber.
 36. The method of claim 35,wherein the tablet is prepared by lyophilizing a liquid suspension orsolution containing suspended or dissolved dry medicament portion in aseparate container.